Evidence for a strong familial component to diabetes in the Pima Indians continues to accrue. Some of the familial influence appears to be transmitted not genetically, but via the intrauterine environment of the pregnant diabetic woman. Despite evidence suggesting the existence of at least one locus for a major diabetes susceptibility gene, evidence for association or linkage with a specific locus remains weak, with the HLA-A locus remaining the best candidate. Although genetic variation at a locus near the insulin gene had previously been shown to have a modest association with non-insulin-dependent diabetes in three racial groups, further studies of this locus suggest there is no role for this gene in diabetes in the Pimas, with the possible exception of homozygosity for one class of alleles. The distributions of other genetic markers have been described and compared with other populations and will be investigated for possible diabetes associations. Improved methods for assessing average glycemia by glycosylated hemoglobin and blood proteins and for assessing diabetic nephropathy by a sensitive immunonephelometric measure of proteinuria have been implemented. These will be used to assess the role of hyperglycemia and other factors in the development of microvascular complications of diabetes. Preliminary analyses suggest that periodontal disease may be much more common and severe in diabetic subjects. Clinically diagnosed gallbladder disease is more common in those with impaired glucose tolerance or diabetes than in those with normal tolerance.